Spinal related complaints are the most common reason for physician visits and healthcare expenditures. Conditions related to back pain account for more hospitalizations than any other musculoskeletal condition and the back is the body part most often involved in work-related disabilities. The spine market is the fastest growing market in orthopedics, creating a unique opportunity to commercialize innovative diagnostic and treatment technologies that are tailored towards specific clinical challenges. One of the greatest challenges for physicians is reaching an accurate diagnosis when faced with certain orthopedic problems. Spinal related sciatic pain can have multiple etiologies, creating diagnostic challenges. Various technologies exist to assist physicians to accurately diagnose these patients, but many are expensive, time consuming and require multiple trips to care providers. A rapid, less costly and accurate diagnosis would greatly benefit the patient. Cytonics Corporation is a privately held biotechnology company that has discovered a novel protein biomarker that not only identifies the source of radicular pain but also specifies an effective treatment course. Objectives during this SBIR Phase I funding period are to further characterize and validate a novel diagnostic biomarker for back pain syndromes that cause radiculopathy. Two Specific Aims are proposed to accomplish these objectives. The first Aim further characterizes a novel protein complex identified by Cytonics as a biomarker of pain caused by low back pain (LBP) syndromes. A standardized antibody based assay will be developed that specifically recognizes this new protein complex biomarker. The second Aim performs a prospective clinical research study to validate the diagnostic assay. Efficient and specific diagnostic tests for neurological root irritation caused by LBP syndromes that also indicate effective treatment strategies will fill an unmet medical need and establish Cytonics as a leader within a large and expanding marketplace. In addition, Cytonics will obtain invaluable information on disease pathogenesis and biochemical targets for the expeditious development of a next generation diagnostic assay and pharmacotherapeutic(s). PUBLIC HEALTH RELEVANCE: Low back pain (LBP) syndromes are one of the most common forms of pain and causes of disability. Americans spend at least $90 billion each year on low back pain, the most common cause of job-related disability and a leading contributor to missed work with an estimated economic burden in the US in hundreds of billions per year. There are many causes of back pain, and proper determination of the source of pain helps guide treatment strategies. Common causes of back pain include disc herniation, spinal stenosis, back muscle strain, and disc degeneration. Pathology of one or more lumbar intervertebral discs is thought to result in severe pain and abnormal sensations radiating from the nerve root down the leg (radiculopathy). Current methods to diagnose radiculopathy and determine proper treatment strategies (steroid injections, surgery, or rest and hope for pain resolution) are inadequate and therefore a very large market and unmet medical need exists. The overall objectives of this clinical proteomics study are to characterize and validate a novel protein complex as a biomarker for radicular pain that also identify patients that will respond to epidural steroid treatment. The objectives of Cytonics Corporation during this SBIR Phase I funding period is to address the following specific aims related to the diagnosis and treatment of LBP syndromes that cause neurological irritation: Aim 1: Further characterize our recently-identified biomarker protein complex and standardize the Cytonics diagnostic assay prototype for neurological root irritation caused by LBP syndromes. A) Additional mass spectrometry and antibody-based approaches will be used to further characterize the novel biomarker protein complex identified in our new preliminary studies. B) Reproducibility, sensitivity and accuracy are essential for robust biomarker detection. Thus, antibody reagents and assay reference standards must be tested to generate the best protocols to maximize diagnostic signal reproducibility and accuracy. These protocols and reagents will be used in all subsequent product development steps and for sample collection kits to be marketed to clinics. Aim 2: Perform a prospective clinical validation study for the Cytonics diagnostic assay. A) Collect patient samples in a multi-center clinical research study. B) Measure levels of the novel protein complex by ELISA generated in Aim 1. Completion of the proposed Specific Aims will enable Cytonics Corporation to create novel and proprietary diagnostic tests that can be rapidly brought to market during a subsequent SBIR Phase II protocol. Efficient and specific diagnostic tests for neurological root irritation caused by LBP syndromes that also indicate effective treatment strategies will fill an unmet medical need and establish Cytonics as a leader within a large and expanding marketplace. In addition, Cytonics will obtain invaluable information on disease pathogenesis and biochemical targets for the expeditious development of a next generation diagnostic assay and pharmacotherapeutic(s).